Project Summary/abstract This application requests support for the PhD Program in Systems Biology at Harvard University. This profoundly interdisciplinary program attracts top students with backgrounds ranging from pure mathematics to medicine, and offers them the resources and support to develop an independent and quantitative approach to important biological questions. The Systems Biology program integrates systems biology research across the whole of Harvard University, including Harvard's main (Cambridge) campus and the basic science departments of Harvard Medical School (HMS) and its teaching hospitals, creating a genuinely unified cross-Harvard program that encourages student creativity and choice of both research area and of future career. The behavior of biological systems is complex and often unpredictable, in ways that profoundly challenge our ability to diagnose and treat diseases or understand the behavior of the world around us. We believe that students who have a deep understanding of both quantitative measurement technologies and mathematical or computational approaches will develop creative new ways to grapple with the complexity of biological systems. The program is also a major vehicle for bringing quantitative and theoretical approaches into problems relevant to the clinic. Since the last submission of this grant, the program has made major strides towards a representative student population: this year, for the first time, female scientists are in the majority in the entering cohort of 8 women and 3 men and applications from underrepresented minorities doubled in 2017-18 compared to previous years. The average time to degree is 5.4 years. The previous grant supported 6 trainees. In this funding period we request support for 8 trainees. The Harvard Systems Biology PhD Program is a pioneering program and an ongoing experiment. The program aims to help students identify biological questions to which an interdisciplinary approach can provide uniquely satisfying answers, and to prepare them to identify and address such questions in their future careers. The program pays particular attention to rigor and reproducibility, training students in the physicochemical basis of the measurements they make and in appropriate techniques, and common pitfalls, in statistical analysis. Training for communication across disciplines and to the lay public is foundational for the Program and is emphasized throughout each student's career.